Efficacy of Pamidronate in the Treatment of Bone Loss Associated With Liver Transplant

Overview

The aims of this study are to prospectively evaluate the efficacy of two intravenous infusions of pamidronate 90 mg, associated with calcium and calcidiol, in the early post-transplant period, on bone loss in liver transplant recipients, and to asses the safety of this treatment.

Full Title of Study: “Prospective, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy of Disodium Pamidronate in the Treatment of Bone Loss Associated With Liver Transplant”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Triple (Participant, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: December 2003

Detailed Description

Patients diagnosed with chronic advanced liver disease awaiting orthotopic liver transplantation will be eligible to take part in this study. Patients excluded from the study will be those younger than 18 years, those receiving a multiorgan transplant or retransplant, or patients with a previous allergy to bisphosphonates. Previous treatment with fluoride, estrogens, selective estrogen receptor modulators or bisphosphonates will be another reason for exclusion, as well as therapy with glucocorticoids during the last 6 months before transplantation. None of the patients will have a previous history of disorders, other than liver disease, known to affect bone metabolism. Study Design and Conduct The study will be a 1-year prospective, randomized, double-blind, placebo-controlled trial conducted at 10 centers in Spain. Immunosuppression All patients will receive microemulsion cyclosporine A (CsA) as primary immunosuppressive agent, in combination with glucocorticoids. Additionally, mycophenolate mofetil will be associated according to the usual clinical practice of each center. In all cases, glucocorticoids will be progressively tapered during the first year. Intervention Patients will receive oral calcium (500 mg twice daily) and oral 25-hydroxy vitamin D (16000 UI every 15 days), after informed consent for the study will be obtained and exploratory screening will be done. Within days 7-12 after engraftment, the recruited transplanted patients (will be randomized to either the experimental or placebo group. Patients of the treatment group will receive a single dose of 90 mg disodium pamidronate within days 7-12 and at 3 months after liver transplantation, diluted in 500 ml of 5% glucose serum and administered as a 4-hour continuous intravenous infusion. Patients of the placebo group will receive 500 ml of 5% glucoside serum infusions. Treatment with oral calcium and vitamin D will be maintained for 1 year after transplantation. Study Endpoints The primary endpoints of the study will be changes in bone mineral density (BMD), quantified by dual energy X-ray absorptiometry (DXA) and safety of pamidronate by recording adverse events. Secondary endpoints will include the incidence of skeletal fractures, by assessment of radiological vertebral fractures (symptomatic and asymptomatic), and the development of nonvertebral fractures. Evaluation Five study visits will be scheduled: before transplantation, within day 7-12 after liver transplantation and at 3, 6 and 12 months after liver transplantation.

Interventions

  • Drug: Disodium pamidronate
    • Single dose of 90 mg disodium pamidronate within days 7-12 and at 3 months after liver transplantation, diluted in 500 ml of 5% glucose serum and administered as a 4-hour continuous intravenous infusion
  • Drug: Placebo
    • 500 ml of 5% glucoside serum infusions within days 7-12 and at 3 months after liver transplantation and administered as a 4-hour continuous intravenous infusion

Arms, Groups and Cohorts

  • Experimental: Pamidronate
    • Single dose of 90 mg disodium pamidronate within days 7-12 and at 3 months after liver transplantation, diluted in 500 ml of 5% glucose serum and administered as a 4-hour continuous intravenous infusion
  • Placebo Comparator: Placebo
    • 500 ml of 5% glucoside serum infusions within days 7-12 and at 3 months after liver transplantation and administered as a 4-hour continuous intravenous infusion

Clinical Trial Outcome Measures

Primary Measures

  • bone mineral density (BMD), quantified by dual energy X-ray absorptiometry (DXA)
    • Time Frame: Change during the 1-year of follow up

Secondary Measures

  • adverse events
    • Time Frame: incidence during 1-year of follow-up
  • incidence of skeletal fractures, by assessment of radiological vertebral fractures (symptomatic and asymptomatic),
    • Time Frame: 1-year of follow-up
  • incidence of nonvertebral fractures
    • Time Frame: 1-year follow-up

Participating in This Clinical Trial

Inclusion Criteria

  • diagnosed with chronic advanced liver disease awaiting orthotopic liver transplantation Exclusion Criteria:

  • younger than 18 years – receiving a multiorgan transplant or retransplant – previous allergy to bisphosphonates – Previous treatment with fluoride, estrogens, selective estrogen receptor modulators or bisphosphonates – therapy with glucocorticoids during the last 6 months before transplantation – previous history of disorders, other than liver disease, known to affect bone metabolism.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Hospital Clinic of Barcelona
  • Collaborator
    • Novartis
  • Provider of Information About this Clinical Study
    • Dr. Miquel Navasa Anadón, Digestive Diseases Institute, Hospital Clinic of Barcelona
  • Overall Official(s)
    • Miquel Navasa, Dr, Principal Investigator, Hospital Clinic i Provincial, Barcelona

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